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Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells.


ABSTRACT: Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.

SUBMITTER: Arner E 

PROVIDER: S-EPMC4681433 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells.

Arner Erik E   Daub Carsten O CO   Vitting-Seerup Kristoffer K   Andersson Robin R   Lilje Berit B   Drabløs Finn F   Lennartsson Andreas A   Rönnerblad Michelle M   Hrydziuszko Olga O   Vitezic Morana M   Freeman Tom C TC   Alhendi Ahmad M N AM   Arner Peter P   Axton Richard R   Baillie J Kenneth JK   Beckhouse Anthony A   Bodega Beatrice B   Briggs James J   Brombacher Frank F   Davis Margaret M   Detmar Michael M   Ehrlund Anna A   Endoh Mitsuhiro M   Eslami Afsaneh A   Fagiolini Michela M   Fairbairn Lynsey L   Faulkner Geoffrey J GJ   Ferrai Carmelo C   Fisher Malcolm E ME   Forrester Lesley L   Goldowitz Daniel D   Guler Reto R   Ha Thomas T   Hara Mitsuko M   Herlyn Meenhard M   Ikawa Tomokatsu T   Kai Chieko C   Kawamoto Hiroshi H   Khachigian Levon M LM   Klinken S Peter SP   Kojima Soichi S   Koseki Haruhiko H   Klein Sarah S   Mejhert Niklas N   Miyaguchi Ken K   Mizuno Yosuke Y   Morimoto Mitsuru M   Morris Kelly J KJ   Mummery Christine C   Nakachi Yutaka Y   Ogishima Soichi S   Okada-Hatakeyama Mariko M   Okazaki Yasushi Y   Orlando Valerio V   Ovchinnikov Dmitry D   Passier Robert R   Patrikakis Margaret M   Pombo Ana A   Qin Xian-Yang XY   Roy Sugata S   Sato Hiroki H   Savvi Suzana S   Saxena Alka A   Schwegmann Anita A   Sugiyama Daisuke D   Swoboda Rolf R   Tanaka Hiroshi H   Tomoiu Andru A   Winteringham Louise N LN   Wolvetang Ernst E   Yanagi-Mizuochi Chiyo C   Yoneda Misako M   Zabierowski Susan S   Zhang Peter P   Abugessaisa Imad I   Bertin Nicolas N   Diehl Alexander D AD   Fukuda Shiro S   Furuno Masaaki M   Harshbarger Jayson J   Hasegawa Akira A   Hori Fumi F   Ishikawa-Kato Sachi S   Ishizu Yuri Y   Itoh Masayoshi M   Kawashima Tsugumi T   Kojima Miki M   Kondo Naoto N   Lizio Marina M   Meehan Terrence F TF   Mungall Christopher J CJ   Murata Mitsuyoshi M   Nishiyori-Sueki Hiromi H   Sahin Serkan S   Nagao-Sato Sayaka S   Severin Jessica J   de Hoon Michiel J L MJ   Kawai Jun J   Kasukawa Takeya T   Lassmann Timo T   Suzuki Harukazu H   Kawaji Hideya H   Summers Kim M KM   Wells Christine C   Hume David A DA   Forrest Alistair R R AR   Sandelin Albin A   Carninci Piero P   Hayashizaki Yoshihide Y  

Science (New York, N.Y.) 20150212 6225


Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription facto  ...[more]

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